Abstract
Background. Immune checkpoint inhibitors (ICIs) have been evaluated as neoadjuvant treatment in urothelial carcinoma (UC) patients, with these agents reporting encouraging pathologic complete response (pCR) rates. Herein, we performed a systematic review and meta-analysis aimed at evaluating the incidence of pCR in UC patients treated with neoadjuvant ICI. Moreover, we investigated the impact of PD-L1 expression in this patient population, exploring the possible role of PD-L1 status as predictive biomarker. Materials and Methods. We retrieved all the relevant trials through PubMed/Medline, Cochrane Library and EMBASE; moreover, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible trials assessed pre-operative ICI in UC patients. Results. Our meta-analysis has highlighted a pooled pCR rate of 36.6% in the overall population; interestingly, pCR was higher in PD-L1 positive compared with PD-L1 negative UCs (49.5% versus 35.1%, respectively). Conclusions. Positive signals emanating from neoadjuvant immunotherapy should encourage the scientific community to persist in the long road toward finding more effective treatments for UC patients.
Highlights
Urothelial carcinoma (UC) is the fourth most commonly diagnosed malignancy worldwide, representing an important cause of cancer-related death [1]; around 25–30% of patients present with muscle-invasive bladder cancer (MIBC) or metastatic urothelial carcinoma (UC) at the time of diagnosis, while about 70–75% of cases are affected by non-muscle-invasive disease [2]
Several clinical trials evaluating the role of immunotherapy in metastatic UC have reported practice-changing results, as witnessed by the approval of five Immune checkpoint inhibitors (ICIs) in the last few years, including pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab, with the JAVELIN Bladder 100 phase III trial recently demonstrating that avelumab maintenance provides superior overall survival versus placebo in patients without disease progression with first-line chemotherapy [7,8]
We reported a promising pathologic complete response (pCR) rate of 36.6% in all-comers, with this proportion rising to 49.5% in PD-L1 positive patients
Summary
Urothelial carcinoma (UC) is the fourth most commonly diagnosed malignancy worldwide, representing an important cause of cancer-related death [1]; around 25–30% of patients present with muscle-invasive bladder cancer (MIBC) or metastatic UC at the time of diagnosis, while about 70–75% of cases are affected by non-muscle-invasive disease [2]. Several clinical trials evaluating the role of immunotherapy in metastatic UC have reported practice-changing results, as witnessed by the approval of five ICIs in the last few years, including pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab, with the JAVELIN Bladder 100 phase III trial recently demonstrating that avelumab maintenance provides superior overall survival versus placebo in patients without disease progression with first-line chemotherapy [7,8]. In patients with localized UC, neoadjuvant cisplatin-based chemotherapy is frequently administered in everyday clinical practice, given the improvement in terms of overall survival reported in several studies and meta-analyses [9,10]. PD-1, PD-L1, and CTLA-4 inhibitors have been assessed as neoadjuvant treatment in UC patients, as monotherapy or in combination with other anticancer drugs, with these agents reporting encouraging pathologic complete response (pCR) rates in early phase clinical trials [14]. The search and review of the articles were evaluated by three authors independently
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